AU - Bushehri, Ata AU - Zare-abdollahi, Davood AU - Alavi, Afagh AU - Dehghani, Alireza AU - Mousavi-mircala, Mohammadreza AU - Khorram Khorshid, Hamid Reza TI - Identification of PROS1 as a Novel Candidate Gene for Juvenile Retinitis Pigmentosa PT - JOURNAL ARTICLE TA - ijmcmed JN - ijmcmed VO - 8 VI - 3 IP - 3 4099 - http://ijmcmed.org/article-1-1102-en.html 4100 - http://ijmcmed.org/article-1-1102-en.pdf SO - ijmcmed 3 ABĀ  - Homozygous mutations of PROS1, encoding vitamin K-dependent protein S (PS), have been reported so far to be associated with purpura fulminans, a characteristic fatal venous thromboembolic disorder. The current work for the first time reports the clinical phenotype in patients with juvenile retinitis pigmentosa harboring a novel likely pathogenic variant in thePROS1 gene. Whole-exome sequencing was performed on the probands of a cohort with inherited retinal disease. Detailed phenotyping was performed, including clinical evaluation, electroretinography, fundus photography and spectral-domain optical coherence tomography. Analysis of whole-exome and Sanger sequencing led to the identification of a homozygous missense substitution (c.G122C:p.R41P) in PROS1 in affected individuals from two unrelated consanguineous families of Persian origin which had classic retinitis pigmentosa with no history of the venous thromboembolic disorder. This variant was segregated, fully congruous with the phenotype in all family members. Consistently, none of 1000 unrelated healthy individuals from the same population carried the mentioned variant, according to the Iranian national genome database (Iranome) and additional in-house exome control data. This study provides inaugural clinical traces for different roles of PS as a ligand for TAM receptor-mediated efferocytosis at the retinal pigmented epithelium; the R41P variant may affect proper folding of PS needed for γ-carboxylation and extra-cellular secretion. That conformational change may also lead to defective apoptotic cell phagocytosis resulting in postnatal degeneration of photoreceptors. CP - IRAN IN - LG - eng PB - ijmcmed PG - 179 PT - Original Article YR - 2019